The overall objective of this research project is to examine the quantitative and qualitative molecular factors that determine the pattern and severity of immune complex mediated injury. The role of immunoglobulin class in the production of experimental nephritis will be studied in a rabbit model of IgG and IgM immune complex disease. It is postulated that biological properties of IgM immune complexes predispose them to the production of focal segmental glomerular lesions. The influence of antigen and immune complex electrical charge as a determinant of immune complex formaton and localization will be investigated in an endogenous model of cationic and an ionic immune complex nephritis in the rabbit. It is postulated that electrical charge might influence the degree to which immune complexes penetrate the glomerular capillary wall and localize either in the subendothelial or subepithelial spaces. Electrical charge also might predispose to in situ immune complex formation by allowing cationic antigens to bind to the anionic glomerular or mesangial wall. All of these molecular factors will be examined in the coming year as part of our research into the pathogenesis of immune complex glomerulonephritis.